Filtration is an important operation in microfluidic devices. A variety of screening, purifying, cleaning, extracting, and like functions that depend on efficient are required for many lab on chip applications. Filtering herein amounts to systematically separating components of a microfluidic stream into filtrate and retentate microfluids, in dependence on a property of the species contained or entrained in the microfluidic stream, to yield higher concentrations of respective species in the filtrate and retentate microfluids than present in the microfluidic stream. To accomplish this, a filter or membrane is typically provided as a selective barrier between a channel for the microfluidic stream and retentate, and the filtrate.
U.S. Pat. No. 6,878,271 teaches the integration of conventional membrane filter technology into microfluidic systems. A variety of filtration systems are shown. It is stated (col. 6, line 35) in U.S. Pat. No. 6,878,271 that a (not illustrated) flow source “may comprise an off-chip syringe pump, a microfabricated peristaltic pump, a microfabricated syringe, or any suitable flow source known in the art, such as those described in U.S. Provisional Patent Application Ser. No. 60/391,868”.
The major problem with filters/membranes and like separators is that they have limited efficiency. In the time the fluid spends at the surface, only some of the fluid will be separated as intended. Because the porosity of most commercially available filters are only in the range of 20% and because most of the microfluidic devices produce the laminar flow in microfluidic channels, 80% of the particles are generally blocked on the surface of the filter. The intended filtrate itself, in combination with the intended retentate, tend to clog pores of filters, further decreasing efficiency. Increasing a shear rate of the flow, and/or the pressure difference across the membrane can help to delay the clogging effect (see U.S. Pat. No. 4,871,462) and may drive intended filtrate through partially clogged perforations, to some degree, but still does not avoid the clogging issue. The higher the pressure drawing the filtrate relative to the retentate, the more quickly the membrane is clogged, resulting in low throughput after the clogging. The higher the pressure drawing the retentate relative to the filtrate, the less clogged the membrane, but less of the fluid that can pass through the separator actually passes through, resulting in lower efficiency. The solution to clogging inherently provided in U.S. Pat. No. 6,878,271 is 1) to provide a large filtration surface area, and 2) to replace the module frequently, but this may not be cost effective, and sometimes may not be practical (for example, if the filter is integrated into a microfluidic system).
Thus many techniques have been developed in the art of filtration; these can be generally categorized into active and passive techniques.1-3 Active separation approaches improve separation using physical forces from external sources such as dielectrophoretic4, optical5-7, magnetic8-11, or acoustic forces.12 However, many of them are expensive, require external fields and power supplies, require pre-processing of the target particles, cannot be easily implemented in multiple levels of separation with high efficiency, and may not easily be miniaturized as required for microfluidic application.
On the other hand, passive separation approaches rely purely on microfluidic phenomena and the interaction of the fluid with the geometries of the microfluidic chip. It includes obstacle induced separation, hydrodynamic filtration13-14, pinched flow fractionation15, inertia and dean flow separation.16-17 Pinches, weirs and posts are common microfluidic obstacles, which are arranged in microfluidic channels to act as filters, decreasing particles of some sizes and densities in certain areas, and increasing the concentration of such particles in other areas. Physical filtering is among the few separation techniques that do not require pre-processing steps or external stimuli such as magnetic or optical fields. U.S. Pat. No. 7,727,399 by Leonard et al. is one example of flow-based separation. When you have a well characterized fluid, and the separation problem is well circumscribed, there are numerous means for improving separation.
It is more difficult to provide a generic, multi-purpose fluid separation system that operates independently of flow rates, volumes, filtrate densities, etc. When designing a general purpose separator, most flow-based separation techniques are of limited use, because when the flow has a different constitution, the efficiency of the system is degraded.
Further to the problem of operational efficiency, there are problems in the art with fabrication, in that bonding of filters to substrates in microfluidic devices can be difficult. Sealing and bonding is especially problematic for thin membranes, which are otherwise very efficient and well suited to microfluidic applications. Especially if the membrane is fragile, as they tend to be if they are high throughput and have small pores. Bonding cannot be easily achieved with very fragile membranes in a cost and time effective way18,19. This limitation becomes even more important (although it may not be impossible to be realized) when multiple levels of membranes are required in order to implement multiple particle fractionations in the same device.
It is known in the art of macroscopic filtration, to recirculate fluid from a retentate stream to the supply of a filter in general, however flow control and loss of pressure across the membrane may require numerous pumps and flow control equipment to orchestrate this recirculation. Additional flow control equipment increases a cost of microfluidic devices. Accordingly there is a need for improved separation techniques for microfluidic devices.